Developmental changes in progenitor cell responsiveness to bone morphogenetic proteins differentially modulate progressive CNS lineage fate

Although multipotent progenitor cells capable of generating neurons, astroc ytes and oligodendrocytes are present within the germinal zones of the brai n throughout embryonic, postnatal and adult life, the different neural cell types are generated within discrete temporospatial developmental windows. This might suggest that multipotent progenitor cells encounter different si gnals during each developmental stage, thus accounting for separate waves o f lineage commitment and cellular differentiation. This study demonstrates, however, that progenitor cell responses to the same class of signals, the bone morphogenetic proteins (BMPs), change during ontogeny, and that these same signals may thus initiate progenitor cell elaboration of several diffe rent lineages. BMPs promote cell death and inhibit the proliferation of ear ly (embryonic day 13, E13) ventricular zone progenitor cells. At later embr yonic (E16) stages of cerebral cortical development, BMPs exhibit a concent ration-dependent dissociation of cellular actions, with either enhancement of neuronal and astroglial elaboration (at 1-10 ng/ml) or potentiation of c ell death (at 100 ng/ml). Finally, during the period of perinatal cortical gliogenesis, BMPs enhance astroglial lineage elaboration. By contrast, olig odendroglial lineage elaboration is inhibited by the BMPs at all stages. Fu rther, application of the BMP antagonist noggin to cultured progenitors pro motes the generation of oligodendrocytes, indicating that endogenous BMP si gnaling can actively suppress oligodendrogliogenesis. These observations su ggest that develop mental changes in neural progenitor cell responsiveness to the BMPs may represent a novel mechanism for orchestrating context-speci fic cellular events such as lineage elaboration and cellular viability. Cop yright (C) 2000 S. Karger AG, Basel.